When attempting to manipulate cellular function, it’s much easier to use the established regulatory pathways rather than building your own. Inserting photoswitches at key points in those pathways let us control cell function with light. The best location for such switches is on the membrane of the cell – easy to measure, open to light sources, and where most of the cell’s regulatory proteins are located.
Voltage gated ion channels, ligand gated ion channels, pumps, actin and tubulin cytoskeleton motor proteins, nuclear hormone receptors, lipids, E3 ligases, and g-protein coupled receptors have all been successfully married to photoswitches so far.
A key molecule is azobenzene, which switches conformation based on exposure to either 500nm or 360nm light.
Tethering ligands to receptors using azobenzene molecules in the tether allows you to directly control bioactivity across a wide spectrum of enzymes. Rapid controlled initiation of downstream signaling can be accomplished with the flick of a light switch.
Medium term goals – the possibility to control things with input signals other than light. Using magnetic fields or ultrasound would be more penetrative. It should also be possible to put molecular motors on proteins.